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Biomedical subjects

H Susskind

Publications and source records attributed to H Susskind.

At least 19 recordsLinked to original sources

Lung inflammation in coal miners assessed by uptake of 67Ga-citrate and clearance of inhaled 99mTc-labeled diethylenetriamine pentaacetate aerosol.

We compared the diffuse lung uptake of 67Ga-citrate, an index of inflammatory lung activity, with the lung clearance of inhaled 99mTc-labeled diethylenetriamine pentaacetate (DTPA) aerosol, an index of pulmonary epithelial permeability, in a group of 19 West Virginia coal miners whose pulmonary status was compatible with coal worker's pneumoconiosis. 99mTc-DTPA clearance alone and 67Ga-citrate uptake alone were measured in nine and five additional subjects, respectively. The objective of this study was to determine if increased 99mTc-DTPA lung clearance was caused by inflammation at the lung epithelial surfaces. Subjects inhaled approximately 150 microCi (approximately 5.6 MBq) of 99mTc-DTPA aerosol, and quantitative gamma camera images of the lungs were acquired at 1-min increments for 25 min. Regions of interest (ROI) were selected to include (1) both lungs; (2) each individual lung; and (3) the upper, middle, and lower thirds of each lung. 99mTc-DTPA clearance was determined from the slopes of the respective time-activity plots for the different ROI. Each subject was intravenously administered 50 miCroCk (1.9 MBq)/kg 67Ga-citrate 48 to 72 h before imaging the body between neck and pelvis. The extent of 67Ga-citrate lung uptake was expressed as the gallium index (GI). Mean radioaerosol clearance half-time (T1/2) for the six nonsmoking coal miners (60.6 +/- 16.0 min) was significantly shorter (p less than 0.001) than for the nonsmoking control group (123.8 +/- 28.7 min). T1/2 for the 12 smoking miners (18.4 +/- 10.2 min) was shorter than for the smoking control group (33.1 +/- 17.8 min), but the difference did not attain statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Increased lung permeability following long-term use of free-base cocaine (crack).

The clearance of inhaled 99mTc DTPA aerosol from the lungs is used as an index of lung epithelial permeability. Using the radioaerosol method, we investigated the effects of long-term "crack" (free-base cocaine) inhalation on lung permeability in 23 subjects. Eighteen control subjects (12 nonsmokers and 6 cigarette smokers) with no history of drug use were also studied. Subjects inhaled approximately 150 muCi (approximately 5.6 MBq) of 99mTc DTPA aerosol and quantitative gamma camera images of the lungs were acquired at 1-min increments for 25 minutes. Regions of interest (ROIs) were selected to include the following: (1) both lungs; (2) each individual lung; and (3) the upper, middle, and lower thirds of each lung. 99mTc DTPA lung clearance was determined from the slopes of the respective time-activity plots for the different RIOs. Radioaerosol clearance half-times (T1/2) for the seven nonsmoking crack users (61.5 +/- 18.3 minutes) were longer than for the seven cigarette-smoking crack users (27.9 +/- 16.9 minutes) and nine cigarette-smoking crack plus marijuana users (33.5 +/- 21.6 minutes). T1/2 for the nonsmoking crack users was significantly shorter (p less than 0.001) than for the nonsmoking control group (123.8 +/- 28.7 minutes). T1/2 for the cigarette-smoking drug users was similar to that of the cigarette-smoking control group (33.1 +/- 17.8 minutes), suggesting a similar mechanism of damage from the smoke of crack and tobacco. From these groups, one nonsmoker and 11 cigarette smokers displayed biexponential 99mTc DTPA clearances, indicative of greater lung injury than found in the usual cases of monoexponential clearance. The upper lungs of all crack users groups cleared faster than the lower lungs. The faster and biexponential clearance properties of inhaled 99mTc DTPA aerosol were the principal functional abnormalities found in all the drug users. In contrast, 19 of 23 crack users had normal spirometry and gas exchange. These results indicate that 99mTc DTPA may provide a sensitive and useful assay to evaluate the physiologic effects of cocaine inhalation in the lung.

Adult

Lung scintigraphy clustering by texture analysis.

The efficiency of texture analysis parameters, describing the organization of grey level variations of an image, was studied for lung scintigraphic data classification. Twenty one patients received a 99mTc-MAA perfusion scan and 81mKr and 127Xe ventilation scans. Scans were scaled to 64 grey levels and 100 k events for inter subject comparison. The texture index was the average of the absolute difference between a pixel and its neighbors. Energy, entropy, correlation, local homogeneity and inertia were computed using co-occurrence matrices. A principal component analysis was carried out on each parameter for each type of scan and the first principal components were selected as clustering indices. Validation was achieved by simulating 2 series of 20 increasingly heterogeneous perfusion and ventilation scans. For most of the texture parameters, one principal component could summarize the patients data since it corresponded to the relative variances of 67%-88% for perfusion scans, 53%-99% for 81mKr scans and 38%-97% for 127Xe scans. The simulated series demonstrated a linear relationship between the heterogeneity and the first principal component for texture index, energy, entropy and inertia. This was not the case for correlation and local homogeneity. We conclude that heterogeneity of lung scans may be quantified by texture analysis. The texture index is the easiest to compute and provides the most efficient results for clinical purpose.

Humans

Effect of PEEP on regional ventilation and perfusion in the mechanically ventilated preterm lamb.

Improvement of gas exchange through closer matching of regional ventilation (V) and lung perfusion (Q) with the application of positive end-expiratory pressure (PEEP) was evaluated in vivo in six mechanically ventilated preterm lambs (107-126 days/145 days gestation). Changes in V and Q were determined from in vivo scintigraphic measurements in four lung regions with inhaled radioactive 81mKr, and infused 81mKr/dextrose and/or [99mTc]MAA as PEEP was applied at 2, 4, and 6 cm H2O in each animal. Dynamic compliance varied between 0.02 and 0.40 ml/cm H2O, which was consistent with surfactant deficiency. As PEEP was increased, the regional distribution of Q shifted from the rostral to the caudal lung regions (p less than 0.02 to less than 0.05), while that of V remained unchanged. Regional V/Q matching improved together with a trend towards improvement of arterial blood gases as PEEP was increased from 2 to 4 cm H2O. Pulmonary scintigraphy offers a noninvasive methodology for the quantitative assessment of regional V and Q matching in preterm lambs and may be clinically applicable to ventilated neonates.

Animals

Heterogeneous ventilation and perfusion: a sensitive indicator of lung impairment in nonsmoking coal miners.

Twenty life-long nonsmoking West Virginia coal-miners participated in a study to amplify the role of focal irregularities on regional ventilation (V) and perfusion (Q) and to develop an improved method for the early detection of coal-workers' pneumoconiosis. Their mean age was 59.3 yr and they averaged 35.2 years' exposure to coal dust. Conventional pulmonary function tests were supplemented by measurement of V, Q and lung volume (V), using radioactive Kr-81m, Tc-99m MAA and Xe-127, respectively, to determine regional abnormalities in lung function. A computer analysis of the regional distributions of V/V, Q/V and V/Q was performed, and their topographical distributions and indices of heterogeneity (HI) computed. V/V and Q/V were significantly reduced in the lower third, and increased in the upper two-thirds of the miners' lungs; V/Q was reduced in the upper half. The miners' V/V and Q/V were more heterogeneous (p less than 0.001) than that of eleven age-matched controls, with mean ventilation HI values of 0.190 +/- 0.027 and 0.133 +/- 0.011, respectively, and mean perfusion HI values of 0.206 +/- 0.022 and 0.164 +/- 0.041, respectively. P(A-a)O2 correlated positively (r = 0.72; p less than 0.001) with ventilation HI. Gas exchange was the most significant functional measurement, being abnormal in 19/20 subjects. In contrast, conventional spirometric measurements were within the predicted normal limits in all but four miners.

Adult

Measurement of lung volume with 81Krm in a dynamic scintigram.

The meaning of 81Krm counts obtained in a dynamic series of gated lung ventilation scans was evaluated in terms of flow rate, lung volume, or the flow/volume ratio. Flow and volume signals were recorded together with scintigraphic events in 29 subjects breathing 81Krm and after its decay, 127Xe as a tracer of lung volume. Gated ventilation scans and respiratory signals were reconstructed. Statistical analyses were carried out for linear regressions between total normalized counts detected by the gamma camera and (1) flow rate, (2) lung volume and (3) flow/volume ratio. Inspiration and expiration were analysed separately. For both isotopes, the best correlation was obtained between counts and lung volume (r greater than 0.93). No correlation was obtained between counts and flow rate or flow/volume ratio. Thus, we conclude that 81Krm count variations in gated scans correlate well with tidal volume.

Humans

Quantitative comparison of regional distributions of inhaled Tc-99m DTPA aerosol and Kr-81m gas in coal miners' lungs.

Regional distributions of deposited Tc-99m diethylenetriamine pentaacetate aerosol (DPTA) and of Kr-81m were compared in the upright lungs of 22 coal miners with nonembolic pulmonary disease. Pixel-by-pixel distributions of Kr-81m and DPTA corrected for lung volume, as well as DTPA/Kr-81m ratios, were determined by computer analysis in each lung and plotted against lung position. DTPA was preferentially deposited in the basal regions of 36/44 lungs. In the same lungs, Kr-81m was preferentially distributed in the apical regions of 18 lungs, bilaterally in six subjects. Similar DTPA and Kr-81m regional distributions throughout both lungs were obtained in only 11 (50%) subjects. No significant correlations were found between regional particle deposition and pulmonary function measurements. The effects of gravity-related lung pressure gradients and ventilation-related particle residence time on the deposition of DTPA may limit its usefulness when quantitative information is required to evaluate subtle changes in ventilation in nonembolic pulmonary patients and for basic studies of ventilation and perfusion.

Administration, Inhalation

Regional distribution of ventilation assessed by Kr-81m scintigraphy employing temporal Fourier transform.

Temporal Fourier analysis was applied to Kr-81m ventilation scintigraphy to determine the amplitude (AMP1) and phase (PHA1) of the first harmonic of a single composite respiratory cycle and to compare regional patterns in subjects with obstructive pulmonary disease (COPD) and nonobstructed subjects. Six nonobstructed subjects, three subjects with small airway disease, six subjects with COPD, and one subject with restrictive disease were investigated. The mean value of the functional PHA1 image (PHA1m) correlated negatively with 1-second forced expiratory volume (FEV1) (r = -0.801, P less than .001), with %FEV1/FVC (r = -0.636, P less than .01) and maximum midexpiratory flow rate (FEF25-75%) (r = -0.723, P less than .002), and correlated positively with residual volume (r = 0.640, P less than .01). PHA1m values for the six subjects with COPD were significantly higher (t = 2.359, P less than .05) than for the ten nonobstructed subjects. Display of phase and amplitude functional images permits a visual evaluation of the regional distribution of ventilation to be made. Regional abnormalities of air flow were detected in obstructed subjects, and the presence of airway obstruction could be predicted. Dynamic ventilation imaging, therefore, appears to be a potentially useful noninvasive technique to assess lung impairment on a localized level.

Adult

Effect of respiratory motion on pulmonary activity determinations by positron tomography in dogs.

The effect of respiratory motion on pulmonary activity determinations by positron emission tomography (PET) was studied in dogs with experimentally created pulmonary emboli (PE). The location of the PE was evaluated by planar 99mTc lung imaging to determine the appropriate sites for transaxial PET scans. PET scans of the lung then were obtained after i.v. injection of 68Ga-labeled microspheres. PET scans were acquired during slow (15 breaths/min) and fast (30 breaths/min) breathing with the same minute ventilation and then postmortem. Lung perfusion patterns were documented by i.v. injection of India ink before sacrifice. Cross sections of the excised lungs were made at the same levels as the PET scans, and eight sections containing 14 perfusion defects were analyzed. The scans obtained during slow breathing consistently showed edge blurring and demonstrated defects less well than scans obtained during fast breathing or postmortem. The normal-to-defect activity ratios during fast breathing and on the postmortem studies were similar and approximately 17% higher (P less than .01) than in scans obtained in the same animals during slow breathing. The results demonstrate the need for motion correction during quantitative analysis of regional lung activity by positron tomography, and suggest that high-frequency respiration at small tidal volumes may be one means for obtaining this correction.

Animals

Obesity alters regional ventilation in lateral decubitus position.

Alterations of regional ventilation were determined as a function of body position in five morbidly obese subjects using 81mKr to assess ventilation (V) and 127Xe at equilibrium to determine lung volume (V). With subjects in seated and supine positions, the left lung contributed an average of 43% of the total V/V. When the apical-basal gradient within each lung was examined in subjects in the seated position, V/V was greatest in the dependent (basal) regions in half of the subjects, whereas the others showed greater V/V near the upper lung regions. All obese subjects preferentially ventilated the nondependent lung in both the left and right lateral decubitus positions. In a control group of three nonobese subjects, V/V was found to be equally distributed between left and right lungs in both the seated and supine positions. In contrast with the results in the obese group, V/V was slightly greater in the dependent lung in both lateral decubitus positions. Although the combination of 127Xe images and He-dilution measurement of functional residual capacity in the lateral decubitus positions indicated a reduction in the volume of the dependent lung of the obese when compared with values in the seated position, other factors affecting the mechanical function of either the diaphragm or the intercostal muscles could also have produced these positional alterations of ventilation.

Adult

Acute response to elastase in sheep lungs measured with Ga-67.

The early inflammatory changes in sheep's lungs were studied with Ga-67 citrate, injected i.v. immediately following intrabronchial instillation of different doses of elastase into the right diaphragmatic lobes of 15 sheep. The elastase-induced lesions in the first five sheep (two received 4,000 units; three got 6,000) were imaged up to seven times in an 8-day period to measure the temporal changes in the lesion and to select the appropriate imaging time; the other ten sheep (800-8,000 units) were imaged once at 52 hr. Localization of Ga-67, as seen on the posterior and right lateral projections, was confined to a well-circumscribed region in the right lung field. The lesion could be detected as early as 4 hr after elastase instillation. It decreased to 60% of its initial area at 4 hr, while the total Ga-67 activity in the sheep remained constant after 52-75 hr. Gallium-67 uptake in the lesion correlated positively with the dose of elastase (r = 0.88, p less than 0.001) and with the reduction in perfusion, as determined 4 wk after the elastase instillation (r = 0.66, p less than 0.05). Early Ga-67 uptake in inflammatory lung lesions could therefore be used as a reliable predictor of the size of the acute elastase-induced inflammatory reaction, as well as of the sequelae involving the regional vascular supply 4 wk later.

Animals

Evaluation of the urinary desmosine radioimmunoassay as a monitor of lung injury after endobronchial elastase instillation in sheep.

Thirty male sheep were treated with varying doses of endobronchial elastase. Urinary excretion of elastin peptides was then measured by desmosine radioimmunoassay and compared with pre-enzyme values. Mean linear intercepts were measured in treated and untreated lobes 4 wk later, and in addition, lung perfusion, ventilation, and volume were measured before enzyme treatment and 4 wk later using radionuclide-imaging techniques. Most of the elevation in urinary desmosine excretion occurred in the first 48 h after elastase administration. The increase in desmosine excretion was positively correlated with: enzyme dose (r = 0.74, p less than 0.01), increase in mean linear intercept (r = 0.61, p less than 0.05), decrease in lung perfusion (r = 0.77, p less than 0.01), and decrease in ventilation (r = 0.58, p less than 0.05). These results demonstrate that the urinary desmosine radioimmunoassay is a reliable index of pulmonary elastin breakdown and of several resultant anatomic and physiologic stigmata of pulmonary emphysema.

Amino Acids

Comparison of airway closure measured in vivo and from single-breath washout curve.

The volume of air trapped (Vat) in alveoli subtended by airways closed at residual volume (RV) was correlated with the volume of air left in the lungs at the start of airway closure (CC) in a clinical study of 13 patients with a variety of pulmonary disorders and 5 normal subjects. Vat was quantitated at RV from the in vivo distribution differences between 127Xe inspired as a bolus and again after equilibrium; CC was measured from the inflection point on the single-breath washout curve at the onset of phase IV. 127Xe activity was measured with a scintillation camera, and activity profiles were obtained for 28-45 consecutive 6.5-mm horizontal lung slices between base and apex. Three well-defined regions were found: A, in the upper lung, all of whose airways remained completely open; B, located above the base and containing both open and closed airways; and C, above the base, all of whose airways were closed. Of the Vat of 0.43 liter for the normals, 41% was located in region C. For the patients, the values were 59% of 0.59 liter. The relationship between the onset of phase IV and regional airway closure was confirmed for normals as well as patients. A statistically significant increase in closure was found for the patients over the normals. Excellent agreement was obtained between Vat/TLC (total lung capacity) and CC/TLC (r = 0.79, P less than 0.001) for normals as well as patients, and CC appears to reflect regional airway closure in both health and disease. Similar excellent agreement was obtained for the normals between lung height with closed airways and CC/TLC (r = 0.88, P less than 0.001). Vat appears to be the most important physiological determinant of phase IV, the value at RV representing the limiting case.

Adult

Sensitivity of Kr-81m and Xe-127 in evaluating nonembolic pulmonary disease.

The relative sensitivities of Kr-81m and Xe-127 in detecting lung ventilation defects was evaluated in 80 patients with nonembolic pulmonary diseases. Krypton-81m ventilation images (500,000 count) were interdigitated with Tc-99m MAA perfusion images; both were compared with Xe-127 images. The distributions of the two gases were also compared on the basis of point-by-point computer analyses. Xenon-127 was found to be more sensitive than Kr-81m in clinical evaluations of scintiphotos--although they were equivalent by computer analyses--in indicating regions of impaired ventilation in patients with obstructive airways disease.

Computers

Reproducibility of ventilation studies.

Differences in ventilation patterns were observed in several instances in two consecutive ventilation studies with 127 Xe and 133Xe gas involving a group of 20 patients with COPD and other pulmonary disorders. Included were differences in the distribution of a tracer gas bolus during the initial inspiration, the distribution of gas tracer after equilibration and during gas washout, artifacts external to the lung, and variations in the half-time for gas washout. The observed discrepancies are clinically significant and could lead to erroneous or ambiguous diagnoses.

Aged

Studies of whole-body retention and clearance of inhaled noble gases.

The in vivo measurements of 127Xe and 79Kr clearance from the whole body indicate five components, with biologic half-times ranging from 13 sec to 17.04 h. The slowest component correlated highly with percent total-body fat, the half-time varying between 7.59 and 17.04 for xenon and between 4.20 and 9.62 h for krypton. The long-term retention was localized to regions of high fat content as determined by the coincidence mode of the whole-body counter and images obtained with the scintillation camera. The estimated dose based on the retention data of this study would indicate increased doses to body fat and gonads as compared with those previously calculated. These increased doses are due to the longer retention of noble gases in fat. After 10-min inhalations of a mixture of 127Xe and air and 79Kr and air, approximately one third of the total 127Xe and one fifth of the total 79Kr were transferred to the body tissues, extrapolated back to the start of gas washout. Of this amount, approximately 13% of the 127Xe and approximately 9% of the 79Kr were associated with the slowest component.

Adipose Tissue